NAXE — 149 ClinVar variants

All ClinVar germline NAXE variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 50 flagged for review →

16 Pathogenic · 7 Likely pathogenic · 3 Conflicting · 20 Benign · 2 Benign/Likely benign · 40 Likely benign · 61 Uncertain significance

Full NAXE gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 50

Variants where the independent computational evidence doesn't line up with the clinical picture — a QC signal for a second look, not a reclassification.

Predictors agree, ClinVar conflicts 1

ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.

NAXE p.Lys245Gln Conflicting Single submitter
encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1

Predictors lean, ClinVar uncertain 42

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.

Predictors split 7

The independent predictors disagree with each other — read with care.

NAXE p.Glu64Ala Uncertain significance Multiple submitters
Inborn genetic diseases
NAXE p.Val68Leu Uncertain significance Multiple submitters
NAXE p.Asp162His Uncertain significance Single submitter
NAXE p.Glu282Val Uncertain significance Single submitter
NAXE p.Leu179Pro Uncertain significance Single submitter
NAXE p.Lys144Gln Uncertain significance Single submitter
encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
NAXE p.Pro235Ser Uncertain significance Single submitter

All NAXE variants

Pathogenic 16

p.Ser43Ter Multiple submitters encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Arg145fs Single submitter
p.Gln157fs Single submitter
p.Gln62Ter Single submitter
p.Gln77fs Single submitter encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Gly189Ser Single submitter encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Leu10fs Single submitter
p.Tyr180fs Single submitter encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Tyr180Ter Single submitter
p.Tyr59Ter Single submitter APOA1BP & NAXE-related disorders
c.516+1G>A No assertion criteria encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy
p.Ala248fs No assertion criteria encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy
p.Ala94Asp No assertion criteria encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy
p.Asp218Val No assertion criteria encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy
p.Gln66Ter No assertion criteria encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy
p.Gly88Trp No assertion criteria encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1

Likely pathogenic 7

c.664+2T>A Multiple submitters encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Arg129Ter Single submitter encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Gln25Ter Single submitter NAXE-related disorder
p.Glu168fs Single submitter encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Leu204Pro Single submitter encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Phe134fs Single submitter encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Trp223Ter Single submitter encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1

Conflicting classifications of pathogenicity 3

p.Lys245Gln Single submitter encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1 ⚠
p.Lys270del Single submitter encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Thr110fs Single submitter encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy

Benign 20

c.291+7G>A Multiple submitters encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
c.292-14G>A Multiple submitters encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
c.517-175A>G Multiple submitters
c.517-219T>C Multiple submitters
c.664+28G>A Multiple submitters encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
c.664+57T>G Multiple submitters
c.664+94G>A Multiple submitters
c.*116C>G Multiple submitters
c.*22T>C Multiple submitters encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Ala266Thr Multiple submitters
p.Glu268= Multiple submitters encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Ile239= Multiple submitters encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Thr281= Multiple submitters encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Thr55= Multiple submitters
p.Val19Leu Multiple submitters encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
c.182+14T>C Single submitter
c.664+114A>T Single submitter
c.665-12C>T Single submitter
c.665-19A>G Single submitter
p.Leu275= Single submitter

Benign/Likely benign 2

c.516+9C>A Multiple submitters
c.517-15C>T Multiple submitters

Likely benign 40

c.516+15T>C Multiple submitters
p.Ala98= Multiple submitters
p.Ile217= Multiple submitters
p.Leu8= Multiple submitters
c.182+11G>A Single submitter
c.182+13C>G Single submitter
c.183-6C>G Single submitter
c.402+14G>A Single submitter
c.402+7A>T Single submitter
c.516+10T>C Single submitter
c.516+14G>A Single submitter
c.664+18G>T Single submitter
c.665-10C>T Single submitter
p.Ala153= Single submitter
p.Ala215= Single submitter
p.Asp177= Single submitter
p.Asp224= Single submitter
p.Cys158= Single submitter
p.Gln82= Single submitter
p.Glu282= Single submitter
p.Glu64= Single submitter
p.Glu71= Single submitter
p.Gly118= Single submitter
p.Gly194= Single submitter
p.Gly209= Single submitter
p.Gly9= Single submitter
p.Ile114= Single submitter
p.Leu154= Single submitter
p.Lys269= Single submitter
p.Lys58= Single submitter
p.Phe78= Single submitter
p.Pro101= Single submitter
p.Pro199= Single submitter
p.Thr102= Single submitter
p.Thr110= Single submitter
p.Thr242= Single submitter
p.Thr252= Single submitter
p.Tyr255= Single submitter
p.Val19= Single submitter
c.183-6C>T No assertion criteria NAXE-related disorder

Uncertain significance 61

p.Arg197Gln Multiple submitters ⚠
p.Arg254Cys Multiple submitters Inborn genetic diseases
p.Glu64Ala Multiple submitters Inborn genetic diseases ⚠
p.Leu86Pro Multiple submitters Inborn genetic diseases ⚠
p.Ser79Arg Multiple submitters ⚠
p.Val68Leu Multiple submitters ⚠
c.291+6_291+7inv Single submitter
c.516+4G>C Single submitter
c.664+4C>G Single submitter
p.Arg129Gly Single submitter encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1 ⚠
p.Arg197Trp Single submitter Inborn genetic diseases ⚠
p.Arg21Trp Single submitter ⚠
p.Arg254His Single submitter ⚠
p.Arg286Cys Single submitter ⚠
p.Asp162His Single submitter ⚠
p.Asp81His Single submitter ⚠
p.Cys158Ser Single submitter ⚠
p.Cys158Tyr Single submitter ⚠
p.Cys283Phe Single submitter ⚠
p.Gln234Arg Single submitter Inborn genetic diseases ⚠
p.Gln288Ter Single submitter
p.Glu178Gly Single submitter ⚠
p.Glu181Lys Single submitter ⚠
p.Glu226Gln Single submitter ⚠
p.Glu282Asp Single submitter ⚠
p.Glu282Val Single submitter ⚠
p.Gly124Cys Single submitter Inborn genetic diseases ⚠
p.Gly253fs Single submitter
p.Gly253Ser Single submitter ⚠
p.Gly259Glu Single submitter ⚠
p.Gly260fs Single submitter
p.Gly9_Leu13del Single submitter
p.Ile163Val Single submitter ⚠
p.Ile187Thr Single submitter ⚠
p.Ile187Val Single submitter ⚠
p.Ile214Thr Single submitter
p.Leu179Pro Single submitter ⚠
p.Leu7Pro Single submitter ⚠
p.Leu8Pro Single submitter Inborn genetic diseases ⚠
p.Lys144Gln Single submitter encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1 ⚠
p.Met104Leu Single submitter ⚠
p.Met1Val Single submitter
p.Pro138Ser Single submitter ⚠
p.Pro164Thr Single submitter ⚠
p.Pro20Gln Single submitter ⚠
p.Pro220Ala Single submitter ⚠
p.Pro235Ser Single submitter ⚠
p.Pro38Leu Single submitter ⚠
p.Ser24Asn Single submitter ⚠
p.Ser2Phe Single submitter ⚠
p.Ser49Pro Single submitter ⚠
p.Ser79Gly Single submitter encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1
p.Thr175Met Single submitter ⚠
p.Thr242Ala Single submitter ⚠
p.Thr281Ile Single submitter
p.Thr281Ser Single submitter Inborn genetic diseases ⚠
p.Thr55Met Single submitter ⚠
p.Trp36Cys Single submitter ⚠
p.Tyr271His Single submitter ⚠
p.Val14Ile Single submitter ⚠
p.Val56Leu Single submitter ⚠